Compounds which have retinoid like activity are well known in the art, and are described in numerous United States and foreign patents and in scientific publications. It is generally known and accepted in the art that retinoid like activity is useful for treating animals of the mammalian species, including humans, for curing or alleviating the symptoms and conditions of numerous diseases and conditions. In other words, it is generally accepted in the art that pharmaceutical compositions having a retinoid like compound or compounds as the active ingredient are useful as regulators of cell proliferation and differentiation, and particularly as agents for treating dermatoses, such as acne, Darier's disease, psoriasis, icthyosis, eczema and atopic dermatitis, and for treating and preventing malignant hyperproliferative diseases such as epithelial cancer, breast cancer, prostatic cancer, head and neck cancer and myeloid leukemias, for reversing and preventing atherosclerosis and restenosis resulting from neointimal hyperproliferation, for treating and preventing other non-malignant hyperproliferative diseases such as endometrial hyperplasia, benign prostatic hypertrophy, proliferative vitreal retinopathy and dysplasias, for treating autoimmune diseases and immunological disorders (e.g. lupus erythematosus) for treating chronic inflammatory diseases such as pulmonary fibrosis, for treating and preventing diseases associated with lipid metabolism and transport such as dyslipidemias, for promoting wound healing, for treating dry eye syndrome and for reversing and preventing the effects of sun damage to skin.
U.S. Pat. Nos. 4,980,369, 5,089,509, 5,162,546, and 5,175,185 disclose acetylene compounds which are substituted by a chromanyl, thiochromanyl or tetrahydroquinolinyl group and by a substituted phenyl or heteroaryl group, having retinoid-like biological activity.
U.S. Pat. Nos. 5,013,744, 5,175,185 and 5,264,456 disclose acetylene compounds which are substituted by an alkylphenyl, alkoxyphenyl or thioalkoxyphenyl group and by a heteroaryl carboxylic acid or carboxylic acid ester group, having retinoid-like biological activity.
U.S. Pat. No. 4,992,468 discloses diphenyl ethylene compounds having retinoid like biological activity. EPO patent application No. 0130795 discloses chroman or thiochroman and phenyl substituted ethylene compounds having retinoid-like biological activity.
U.S. Pat. Nos. 5,006,550, 5,015,658, 5,130,335, 5,143,159, and 5,231,113 disclose esters and thioesters of substituted phenol compounds (such as of para-hydroxy benzoic acid) with 5,6,7,8-tetrahydronaphthoic acid, chromanoic acid or thiochromanoic acid, having retinoid like biological activity.
U.S. Pat. No. 5,037,825 discloses compounds having retinoid-like biological activity where a condensed heterocyclic ring such as a thiochroman is connected to a substituted phenyl ring with an ethylene, or amide (CONH) bridge. An article in Journal of American Academy of Dermatology by Sporn et. al. and an article in Journal of Medicinal Chemistry, 1988, 31, 2182-2193 (Kagechika et al.) also disclose compounds of retinoid-like biological activity where a tetrahydronaphthalene, chroman or thiochroman moiety and a benzoic acid moiety are connected by an amide (CONH) bridge.
Several co-pending applications and recently issued patents assigned to the assignee of the present application, are directed to further compounds having retinoid-like activity.